DESCRIPTION (Applicant's Description): Age-related macular degeneration (AMD) is the leading cause of blindness in people over the age of 65 in the United States. About 10 percent of the U.S. population will develop AMD and 1 percent may suffer from the more advanced, exudative form of the disease that leads to severe visual impairment. The basic mechanism involved in the development of this disease is not clearly understood. One of the most common manifestations of this disease, however, is the deposition of materials that are not adequately removed from the retinal pigment epithelium-Bruch's Membrane interface. Several recent reports and some preliminary data from our laboratory have suggested abnormalities of the choroidal circulation in AMD. These reports are of great interest because this circulation supplies all metabolites and removes all waste products from the outer retina. An abnormal choroidal circulation could have a role in the process that leads to the accumulation of these abnormal substances. In addition, a decreased choroidal vascular supply could also lead to ischemia and hypoxia of the outer retina and this could be associated with the development of choroidal neovascularization, a blinding complication of AMD. The main aim of this application is to use the state-of-the-art non-invasive technique of laser Doppler flowmetry to investigate whether choroidal blood flow and its regulation are abnormal in AMD, and whether a more abnormal choroidal circulation is associated with a higher risk of developing choroidal neovascularization and the more advanced and blinding stages of AMD. A better understanding of the mechanisms associated with the development of AMD could, in the long run, help us devise new treatment strategies for this devastating disease. In addition, the knowledge gained through this investigation could also help in the identification of patients at risk of developing choroidal neovascularization, thus enabling earlier treatment.